Molecules of RNA are transcribed from DNA. RNA molecules are relatively short compared to DNA molecules. RNA transcripts that direct the synthesis of protein molecules are called messenger RNA (mRNA) molecules, while other RNA transcripts serve as transfer RNAs (tRNAs) or form the RNA components of ribosomes (rRNA) or smaller ribonucleoprotein particles.
The amount of RNA-made from a particular region of DNA is controlled by gene regulatory proteins that bind to specific sites on DNA close to the coding sequence of a gene. In any cell at any given time, some genes are used to make RNA in very large quantities while other genes are not transcribed at all. For an active gene thousands of RNA transcripts can be made from the same DNA segment in each cell generation. Because each mRNA molecule can be translated into many thousands of copies of a polypeptide chain, the information contained in a small region of DNA can direct the synthesis of millions of copies of a specific protein.
In eukaryotes, a primary RNA transcript is synthesized; this transcript contains both introns and exons. Intron sequences are cut out and exon sequences on either side of an intron are joined together by RNA splicing.
The translation of mRNA into protein depends on a set of small RNA molecules known as transfer RNAs (tRNAs), each about 80 nucleotides in length. A tRNA molecule has a folded three-dimensional conformation that is held together in part by noncovalent base-pairing interactions like those that hold together the two strands of the DNA helix. In the single-stranded tRNA molecule, however, the complementary base pairs form between nucleotide residues in the same chain, which causes the tRNA molecule to fold up in a unique way.
The codon recognition process by which genetic information is transferred from mRNA via tRNA to protein depends on the same type of base-pair interactions that mediate the transfer of genetic information from DNA to DNA and from DNA to RNA. The mechanics of ordering the tRNA molecules on the mRNA require a ribosome. Each ribosome is a large protein-synthesizing machine on which tRNA molecules position themselves so as to read the genetic message encoded in an mRNA molecule. The ribosome first finds a specific start site on the mRNA that sets the reading frame and determines the amino-terminal end of the protein. Then, as the ribosome moves along the mRNA molecule, it translates the nucleotide sequence into an amino acid sequence one codon at a time, using tRNA molecules to add amino acids to the growing end of the polypeptide chain. When a ribosome reaches the end of the message, both it and the freshly made carboxyl end of the protein are released from the 3′ end of the mRNA molecule into the cytoplasm.
Although most tRNAs are initially synthesized as a larger precursor RNA, an RNA molecule has been shown to play the major catalytic role in an RNA-protein complex that recognizes these precursors and cleaves them at specific sites. A catalytic RNA sequence also plays an important part in the life cycle of many plant viroids. Most remarkably, ribosomes are now suspected to function largely by RNA-based catalysis, with the ribosomal proteins playing a supporting role to the ribosomal RNAs (rRNAs), which make up more than half the mass of the ribosome. The large rRNA by itself, for example, has peptidyl transferase activity and catalyzes the formation of new peptide bonds.
The development of compositions and methods for modulation of RNA would be of great benefit in modulating numerous cellular processes and in the treatment of disorders.